Co-delivery of LIGHT expression plasmid enhances humoral and cellular immune responses to HIV-1 Nef in mice

Abstract

The immunogenicity and efficacy of a DNA vaccine can be greatly enhanced when a gene adjuvant is used. LIGHT, a member of TNF superfamily, can function as a costimulatory molecule for human naïve T cells to proliferate and can be a potential gene adjuvant. In the current study, the eukaryotic expression plasmid pcDNA-nef was constructed by inserting a full-length nef gene into pcDNA3.1(+), and an in vitro transfection experiment suggested that the nef gene could be expressed successfully in mammalian cells. BALB/c mice were immunized with HIV-1 nef DNA vaccine plasmids alone or in combination with LIGHT expression plasmids, and the specific humoral and cellular immune responses were measured. The data showed that HIV-1 nef DNA vaccine plasmids could induce anti-Nef antibodies, Nef-specific lymphocyte proliferation and CTL activity, whereas stronger specific immune responses were induced in mice when co-immunizing with HIV-1 nef DNA vaccine plasmids and LIGHT expression plasmids, suggesting that the eukaryotic expression vector encoding HIV-1 nef is capable of inducing specific immune responses towards HIV-1 Nef and that LIGHT could be considered as a gene adjuvant for HIV-1 DNA vaccination.

Immune Responses of Piglets Immunized by a Recombinant Plasmid Containing Porcine Circovirus Type 2 and Porcine Interleukin-18 Genes

“…Thus, development of new-generation vaccines is necessary to control PCV2 infection. Direct injection of plasmid DNA has been used as a promising approach to protect animals and humans against pathogens (34,35). DNA vaccines against PCV2 have been investigated, which often have limited efficacy and need two or three immunizations to achieve a good level of immunity (1,3,8).…”

Construction of a Prokaryotic Expression Vector harboring Two HIV-1 Accessory Genes

“…However, the issue of finding complementary or alternative treatment and prevention strategies still persists. Among numerous HIV genes examined for generation of immunogenic recombinant DNA and proteins, the highly-conserved HIV-1 accessory protein Nef has been widely regarded as a highly immunogenic candidate for development of therapeutic vaccines (14)(15)(16)(17). This is mainly attributed to the main role of Nef in HIV pathogenesis via downregulation of cell-surface expression of multiple membrane-associated proteins, enhancement of virion infectivity, stimulation of viral replication, interference of cellular 15/ Nikyar and colleagues polymerase.…”

“…signal transduction, and manipulation of the apoptosis mechanism (14). On the other hand, Vpr has been known as a crucial component of HIV pathogenicity and progression.…”

Improving the potency of DNA vaccine encoding HIV-1 Nef antigen using two endogenous adjuvants in mouse model

“…One study indicated that anti-Nef antibodies in mice immunized with pBN-Nef were detected within four weeks after the last immunization, whereas mice immunized with pCGE2-Nef had poor anti-Nef antibodies (45). Other data showed that HIV-1 Nef DNA vaccine (pcDNA-Nef) could induce anti-Nef antibodies and Nef-specifi c CTL activity, but stronger specifi c immune responses were stimulated in mice receiving pcDNA-Nef along with LIGHT expression plasmid (LIGHT, a member of TNF superfamily), suggesting that the LIGHT could be considered as a gene adjuvant for HIV-1 DNA vaccination (46). Herein, we also showed that Gp96 as an adjuvant could increase immune responses induced by pcDNA-Nef regimen.…”